Human immunodeficiency virus (HIV) is a retrovirus and a major human pathogen. Infection of individuals leads to eventual immune disfunction. Simian immunodeficiency virus (SIV) is a virus associated with some African primates. When introduced into Asian monkeys, such as Rhesus macaques, a disease similar to acquired immunodeficiency syndrome (AIDS) is induced. The focus of the proposed research is to examine the HIV-1 and SIV proteins that are known or proposed to function in virus exit from, or entry into, cells. This study will center on the role of three gene products in virus replication and pathogenesis. Using genetic and molecular approaches, the Panganiban research group will examine the function of the transmembrane peptide of the envelope glycoprotein (Env- gp), and, in the case of HIV-1, the role of the Vpu gene product. Experiments will be carried out to delineate the function of the cytoplasmic tail of the Env-gp, to examine the viral determinants of correct association between Env-gp and the virus particle, and to examine the role of the Env-gp fusion domain in cells susceptible to HIV and SIV infection. Using complementary approaches, the Panganiban group will determine the function of the Vpu proteins in virus replication and identify viral or cellular genes that interact with these two proteins.